Biomedical subjects
Publications and source records attributed to M N Boĭchenko.
A variety of approaches to creating vaccines against the HIV-infection are discussed in the paper. It is demonstrated that vaccines can be used both for treatment and prevention. They can be synthetic, DNA-vaccines and vector-type ones based on the attenuated recombinant strain of Salmonella. Apart from gp120, reverse transcriptase and tat-gene products can be used as the antigen.
Designing of a therapeutic vaccine for patients with chronic hepatitis B is a task of contemporary medicine. The natural way of administering the vaccine is the most attractive and inexpensive immunization variant. The use of attenuated strain Salmonella as a carrier of the virus antigen fits the purpose. With this idea in mind, the potentialities of the recombinant attenuated strain Salmonella Enteritidis E-23/pKHBc to replicate in the intestine, mesenteric nods and spleen of mice and to stimulate the immune response to HBc-antigen after its rectal administration (as suppositories) in mice were investigated. It was shown that the recombinant strain is discharged from the intestine within 6 hours after immunization, whereas, it is discharged on day 2 after immunization from the lymphatic nods and is traced there during the 5 subsequent days. Besides, the recombinant strain also possessed the possibility to persist in the spleen of mice for 42 days and to induce there the formation of antibodies to HBc-antigen.
Studies of human microflora in health and disease and during exposure to professional and ecological factors is a traditional problem solved for many years by staff members of Department of Microbiology with Virology and Immunology, I. M. Setchenov Moscow Medical Academy. The purpose of research is to develop methods and means for diagnosis and prevention of human microbiocenosis disorders. Fundamental and applied research in cooperation with prophylactic and clinical institutions and departments yielded data contributing to solution of many pressing problems in prevention and diagnosis of infectious diseases.
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The Salmonella typhimurium B-2/1 double mutant with cya and crp mutations was obtained by a recombination process. The mutant exhibited a low virulence and inability to utilize citrate. In terms of these properties, the mutant differs from the wild-type strain. The mutant is able to persist in the body of mice, cattle, and monkeys, provoking the immune response to its oral administration.
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To study the role of cAMP in the virulence of S. typhimurium, cAMP-producing plasmid pTG 4 was transferred to cAMP-deficient S. typhimurium mutant. The transfer of the plasmid enhanced the virulence of the microorganisms due to the increased destruction of macrophages and the intensified multiplication of salmonellae in the spleen of mice.
The changes in cAMP levels in spleen macrophages of mice infected with low-virulent and virulent Salmonella strains and the effect of propranolol on Salmonella reproduction in the spleen, and the outcome of Salmonella-induced infection have been studied. A persistent increase in cAMP levels in spleen macrophages during Salmonella infection caused by virulent Salmonella strains has been demonstrated. Low-virulent Salmonella strains failed to cause the elevation of cAMP levels in spleen macrophages. Propranolol injection to mice prevented intensive Salmonella reproduction in the spleen and diminished the animal mortality rate.
The effect produced on the course of Salmonella infection in mice by the removal of peritoneal macrophages with agarose has been studied. Peritoneal macrophages have been shown to control the multiplication of faintly virulent and virulent S. typhimurium strains in the spleen of mice. In immune mice the elimination of the virulent strain of the causative agent of superinfection may occur without the control of peritoneal macrophages.
To reveal the influence of cyclic adenosine monophosphate (cAMP) on the completion of the phagocytosis of salmonellae, the influence of insulin and isoproterenol on the phagocytic activity of peritoneal macrophages obtained from mice infected with S. typhimurium strains differing in virulence was studied in vitro. The study showed that isoproterenol, while increasing the intracellular content of cAMP, suppressed the bactericidal properties of macrophages with respect to salmonellae, whereas insulin decreased the level of cAMP in the cells and thus facilitated more rapid and complete digestion of ingested bacteria irrespective of their virulence.
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The dynamics of changes in the level of intracellular cyclic AMP in nonimmune and immune macrophages in the process of the phagocytosis of S. typhimurium virulent strain, its heated variant and its mutant with low virulence was studied. A transient increase in the level of cyclic AMP was shown to occur during the first 30 minutes of phagocytosis; this increase did not depend on the kind of the phagocytized object and on the activity of macrophages and neither had it any influence on the outcome of phagocytosis. The virulent strain also induced the three-fold increase of the level of cyclic AMP in nonimmune macrophages prior to their disintegration caused by the cytopathogenic action of the microorganism. In immune macrophages the virulent strain did not induce the secondary increase of the level of cyclic AMP.
The effect of a virulent S. typhimurium strain and its cAMP-deficients mutant on the level of cAMP in macrophages in the process of phagocytosis has been studied. The virulent strain has been shown to induce the 3-fold increase of the level of cAMP in macrophages, while the mutant renders no such effect.
The behavior of c-AMP-deficient S. typhimurium mutants in the culture of peritoneal macrophages of white mice and the antibacterial activity of immune macrophages obtained from mice previously immunized with c-AMP-deficient S. typhimurium mutants were studied; c-AMP-deficient mutants were shown to have a lesser cytotoxic effect on macrophages than the initial virulent strain, while retaining their capacity for intracellular proliferation. Immune macrophages acquired the ability to withstand the cytotoxic action of the virulent strain.